efficacy and safety of stempeucel® in patients with critical limb ischemia (cli) due to peripheral arterial disease

Conditions: Critical Limb Ischemia; Peripheral Arterial Disease

Summary: the goal of this observational, practice-based feasibility study is to observe the efficacy and safety of intramuscular administration of stempeucel® in malaysian patients with critical limb ischemia (cli) due to peripheral arterial disease. the main questions it aims to answer are: * can intramuscular administration of stempeucel® reduce symptoms of cli due to peripheral arterial disease while improving the healing rate and functional outcomes? * does intramuscular administration of stempeucel® causes any serious adverse events in cli due to peripheral arterial disease patients? study patients will be assessed by the pi before administering the stempeucel® for any other organ with inflammation. the study patients will also be followed up to the duration of 1 year after study treatment administration for safety and efficacy assessment.

title: an observational, practice-based, open label, feasibility study to observe the efficacy and safety of intramuscular administration of stempeucel® in malaysian patients with critical limb ischemia (cli) due to peripheral arterial disease study design: single arm, practice-based, feasibility study study duration: estimated duration for the main protocol (e.g. from starts of screening to last subject processed and end of the study) is approximately 18 months study center: universiti kebangsaan malaysia medical centre (ukmmmc), jalan yaacob latif, bandar tun razak, 56000 kuala lumpur, wilayah persekutuan, malaysia objectives: to observe the efficacy and safety of stempeucel® (adult human bone marrow derived, cultured, pooled, allogeneic mesenchymal stromal cells) in malaysian patients with critical limb ischemia (cli) due to peripheral arterial disease. investigational medicinal product description • ex-vivo cultured allogeneic mesenchymal stem cells (mscs) supplied in cryo-bags consisting of 150 or 200 million, suspended in 50 ml of plasmalyte a containing 1.5% human serum albumin (hsa) and 3% dimethyl sulfoxide (dmso). dosage • dosing of stempeucel® is based on body weight. the recommended dose is 2 million cells/kg body weight. administration • 40 - 60 injections administered as 0.6 ml/kg (200 million bag) or 0.8 ml/kg (150 million bag) intramuscularly into different points on the muscle. additional injections of 2 ml (200 million bag) or 3 ml (150 million bag) administered around the ulcer number of subjects: 10 patients data analysis data management: * electronic case record form (ecrf) will be used for data entry. * oracle clinical (or other suitable alternatives with audit trail) will be used for data management. statistical method: * the spss® package (ibm inc., usa, version 22) will be used for statistical evaluation. * all patients in the study with relevant efficacy and safety data will be considered for the analysis. * efficacy analysis will be done using gee (generalized estimating equations) method or paired t test as appropriate. * adverse events monitored using information voluntarily disclosed by the patients and as observed by the pi will be summarized descriptively by total number of ae(s). * aes will be categorized as: all aes, all treatment-emergent aes, all severe aes, treatment-related aes and severe treatment-related aes. these events will be reported as appropriate and summarized.

Eligibility criteria:
inclusion criteria: * patients between 18-65 years old * patients diagnosed with atherosclerotic peripheral arterial disease * patients not eligible for or have failed surgical or percutaneous revascularization (no option patients) * patients with at least one ulcer (between 0.5 to 10 cm2 size) * ankle brachial pressure index (abpi) ≤ 0.6 (toe brachial index (tbi) if abpi out of range; tbi ≤ 0.5) * patients who are able and willing to provide consent and agrees to comply with study procedures and follow-up evaluations exclusion criteria: * patients diagnosed with buerger's disease by shionoya criteria * patients eligible for surgical or percutaneous revascularization * patients with a history of participating in another stem cell trial or therapy within 3 months * patients who are unsuitable to participate the clinical trial as determined by investigators

Keywords: critical limb ischemia peripheral arterial disease bone marrow-derived mesenchymal stem cell